Induced hyperlipaemia and immune challenge in locusts

Injections of immunogens, such as β-1,3-glucan or lipopolysaccharide (LPS), bring about a marked hyperlipaemia with associated changes in lipophorins and apolipophorin-III in the haemolymph of Locusta migratoria. These changes are similar to those observed after injection of adipokinetic hormone (AKH). The possibility that endogenous AKH is released as part of the response to these immunogens is investigated using passive immunisation against AKH-I, and measurement of AKH-I titre in the haemolymph after injection of immunogens. The data presented show that, despite the similarity of the changes brought about by the presence of immunogens in the haemolymph to those brought about by AKH, there is no release of endogenous AKH after injection of laminarin or LPS. A direct effect of the immunogens on release of neutral lipids by the fat body cannot be demonstrated in vitro, and the mechanism by which hyperlipaemia is induced during immune challenge remains uncertain

Differential Effect of γ-radiation-induced Heme Oxygenase-1 Activity in Female and Male C57BL/6 Mice

Ionizing radiation produces reactive oxygen species, which exert diverse biological effects on cells and animals. We investigated alterations of heme oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti-oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain after whole-body γ-irradiation with 10 Gy (1-7 days) as well as in the lung after whole-thorax γ-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most significant alteration of HO activity was observed in the liver, which elevated 250% in males. NPSH level in female liver was increased on the 5th-7th days but decreased in males on the 3rd day. In the lung, the elevation of HO activity in both sexes and the pattern of NPSH change were similar to that of the liver. On the other hand, the increase of HO activity on the 16th week and the decrease of NPSH level on the 2nd week were observed only in male lung after WTI. This study shows that the liver is the most sensitive tissue to γ-irradiation-induced alterations of HO activity in both female and male mice. In addition, there exists significant differential effect of γ-irradiation on anti-oxidant system in female and male mice

Cultured adult rat jejunal explants as a model for studying regulation of CYP3A

Enzymes within the CYP3A subfamily are major Phase I drug-metabolizing enzymes present in hepatocytes and small bowel enterocytes. These enzymes are highly inducible in the liver by many structurally diverse compounds, including a number of commonly used medications. Studies indicate that CYP3A enzymes present in small bowel enterocytes are also inducible. However, the regulation of CYP3A enzymes in this tissue has not been well characterized, in part because in vivo studies are difficult, especially in humans. Our goal was to develop an in vitro model to study the regulation of CYP3A in enterocytes. To this end, we defined culture conditions under which adult rat jejunal explants maintained viable appearing villi for 21 hr. When dexamethasone, the prototypical inducer of CYP3A1 in rat hepatocytes, was added to the culture medium, there was a time-dependent induction of CYP3A1 mRNA and CYP3A protein in explant enterocytes which was essentially indistinguishable from the time course of induction of CYP3A1 mRNA and protein in enterocytes in vivo. This effect of dexamethasone appeared to be specific since dexamethasone had no consistent effect on the explant concentration of another enterocyte specific mRNA, intestinal fatty acid binding protein. Using this explant culture model, we found that CYP3A1 mRNA was also inducible by clotrimazole but we were unable to detect induction by rifampicin or troleandomycin. Our observations suggest that jejunal explants may provide an appropriate model for the study of the regulation of CYP3A and other drug-metabolizing enzymes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30618/1/0000258.pd

A Comparison of Pregnancies That Occur Before and After the Onset of Chronic Fatigue Syndrome

Background Many women with chronic fatigue syndrome (CFS) fear that pregnancy will worsen their condition, increase the risks of maternal complications of pregnancy, or threaten the health of their offspring. Little empirical evidence, however, has been published on this matter. Methods A detailed questionnaire was administered to 86 women regarding 252 pregnancies that occurred before or after the onset of CFS and the outcomes of these pregnancies were observed. Results During pregnancy, there was no change in CFS symptoms in 29 (41%), an improvement of symptoms in 21 (30%), and a worsening of symptoms in 20 (29%) of 70 subjects. After pregnancy, there was no change in CFS symptoms in 21 (30%), an improvement of symptoms in 14 (20%), and a worsening of symptoms in 35 (20%) of the subjects. The rates of many complications were similar in pregnancies occurring before the onset and in those occurring after the onset of CFS. There was a higher frequency of spontaneous abortions in the pregnancies occurring after, vs before, the onset of CFS (22 [30%] of 73 pregnancies after vs 13 [8%] of 171 before; P<.001), but no differences in the rates of other complications. Developmental delays or learning disabilities were reported more often in the offspring of women who became pregnant after, vs before, the onset of CFS (9 [21%] of 43 children vs 11 [8%] of 139 children; P = .01). Conclusions Pregnancy did not consistently worsen the symptoms of CFS. Most maternal and infant outcomes were not systematically worse in pregnancies occurring after the onset of CFS. The higher rates of spontaneous abortions and of developmental delays in offspring that we observed could be explained by maternal age or parity differences, and should be investigated by larger, prospective studies with control populations. Chronic fatigue syndrome (CFS) is a debilitating illness characterized by fatigue, muscle and joint aches, headache, sleep disruption, and cognitive impairment that, by definition, last at least 6 months.1 Studies in the past decade indicate that an underlying biological process involving the central nervous system and the immune system is present.2 Typically, the onset of CFS is sudden, and the chronic debility that follows usually lasts many years.3 Many patients who seek medical care for CFS are women in their childbearing years who want to become pregnant but are fearful of possible adverse consequences for themselves and their offspring. There is a paucity of information describing the reciprocal effects of pregnancy and CFS. Does being pregnant improve, worsen, or leave unchanged the symptoms of CFS? Do women who have CFS experience more frequent complications of pregnancy? Is the health of the offspring affected by CFS? One could speculate that the physical and mental stress of being pregnant adversely affects a woman's symptoms, particularly the fatigue. However, anecdotal evidence from one of the author's (A.L.K.) practice indicates that some patients with CFS feel better during pregnancy, particularly in the first trimester. To address these questions, we asked the female patients followed in the practice to provide detailed information about all of their pregnancies

A Model of Brain Arteriolar Oxygen and Carbon Dioxide Transport during Anemia

Existing experimental and theoretical evidence suggests that precapillary diffusion of O2 and CO2 occurs between arterioles and tissue under normal physiologic conditions. However, limited information is available on arteriolar gas transport during anemia. With use of a mathematical model of an arteriolar network in brain tissue, anemic hematocrits of 35, 25, and 15% were modeled to determine the effect of anemia on the exchange, the change in the equilibrium tissue O2 and CO2 tensions, and the increase in blood flow needed to restore tissue oxygenation. We found that the blood Po2 exiting the network fell from 66 mm Hg normally to 48 mm Hg during the severest anemia. Concurrently, the equilibrium tissue O2 tensions dropped from 44 to 23 mm Hg. For CO2 the exit blood Pco2 was 58 mm Hg for a 15% hematocrit, an increase of 4 mm Hg from the normal value, and equilibrium tissue Pco2 increased from 56 to 61 mm Hg. Blood flow increases from normal values necessary to offset the effects of the decreased O2 delivery to the tissue were 26, 86, and 222%, respectively, for hematocrits of 35, 25, and 15%. We compared our model results with recent experimental studies that have suggested that the amount of O2 diffusion is much higher than predicted values. We found that these experimental O2 gradients are three to four times larger than theoretical. </jats:p